Multipole corrections to account for structure and proximity effects in group contribution methods: Octanol-water partition coefficients
Journal
Journal of Physical Chemistry A
Journal Volume
104
Journal Issue
30
Pages
7099-7105
Date Issued
2000
Author(s)
Abstract
We propose a new method to correct for structure and proximity effects that are not generally accounted for in group contribution models. Molecular orbital calculations for isolated molecules are performed to obtain the net charge and dipole moment on each group within the molecule. These group multipoles, which vary as a result of the presence of proximate groups, are used as the basis for corrections to simple group contribution methods. We have applied this method to our recently developed GCSKOW model to predict the octanol−water partition coefficients (KOW) for complex molecules. We studied this simple, theoretically based method with a total of 450 solutes, including five pharmaceutical compounds. The root-mean-square (RMS) deviation in the log10 KOW calculated from the GCSKOW model with these multipole corrections is found to be 0.18 (which leads to a mean error of 52% in KOW), compared with a RMS deviation of 0.44 (177%) when no correction is made. This simpler approach is more accurate than the KOW−UNIFAC model (RMS of 0.28 or an error of 92% in KOW for 344 compounds) and is comparable to the ClogP model (0.18 or 52%), which heretofore had been considered to be the most accurate predictive method for octanol−water partition coefficients.
SDGs
Type
journal article